Host: The Japanese Pharmacological Society
Name : The 95th Annual Meeting of the Japanese Pharmacological Society
Number : 95
Location : Fukuoka
Date : March 07, 2022 - March 09, 2022
The communication between the brain, immune and vascular systems is a key contributor to the onset and progression of neurological diseases. We discovered the coagulation factor fibrinogen as a blood-derived driver for neuroinflammation and inhibitor of repair in a wide range of neurologic diseases, such as multiple sclerosis, Alzheimer's disease and brain trauma. We showed that fibrinogen is necessary and sufficient for neurodegeneration and a new culprit for microglia-mediated oxidative stress-dependent spine elimination and cognitive impairment. By developing Tox-Seq, we reported the oxidative stress innate immune cell atlas in neuroinflammation. We developed cutting-edge imaging tools to study brain network synchronization and the neurovascular interface. We discovered a first-in-class fibrin-targeting immunotherapy to selectively target inflammatory functions of fibrin without interference with clotting with potent therapeutic effects in autoimmune- and amyloid-driven neurotoxicity. High throughput drug screens identified small molecule compounds to block fibrin-induced activation of microglia with therapeutic effects in neuroinflammatory disease. These findings could be a common thread for the understanding of the etiology, progression, and new treatments for neurologic diseases with neuroimmune and cerebrovascular dysfunction. As fibrin is a global activator of toxic innate immune responses in the brain and periphery, these studies could provide the basis for the development of a new class of therapeutics for autoimmune and inflammatory diseases1.
1. Akassoglou, K. The immunology of blood: Connecting the dots at the neurovascular interface. Nat Immunol 2020, 21:710-712
